ORIGINAL ARTICLE
Stereotactic radiosurgery and radiotherapy in benign
intracranial meningioma
Eman Eldebawy
a,*
, Amr Mousa
a, Wael Reda
b, Mahmoud Elgantiry
aa
Radiation Oncology Department, National Cancer Institute, Cairo University, Egypt
b
Neurosurgery Department, Ain Shams University, Egypt Received 12 May 2011; accepted 21 June 2011
Available online 22 October 2011
KEYWORDS Stereotactic; Radiosurgery; Meningioma; Hypo-fractionated; Benign
Abstract Purpose: To investigate the role of stereotactic radio surgery (SRS) and hypo-fractionated stereotactic radiotherapy (SRT) in treatment of benign intracranial meningioma. Patients and methods: Between 2003 and 2010, 32 patients with a median age of 44 years (range 21–67 years) were treated with SRS (n = 19), and hypo-fractionated SRT (n = 13) for intracranial meningioma. Fourteen patients underwent SRS or SRT as their primary treatment, while 18 patients underwent post operative SRS or SRT (PORT). Cumulative progression free survival, overall cumulative survival, toxicity and symptomatology were evaluated.
Results: The median follow up period was 39 months (range 6–72 months). The 5 year overall sur-vival and progression free sursur-vival were 90 ± 5% and 94 ± 4% after SRT or SRS respectively. Symptoms were improved or stable in 94% of patients. Acute toxicity was mild, and was seen in 41% of patients. Clinically significant late morbidity or new cranial nerve palsies did not occur. Conclusion: Stereotactic radio surgery (SRS) and hypo-fractionated stereotactic radiotherapy (SRT) are effective and safe treatment modality for local control of meningioma with low risk of sig-nificant late toxicity. In case of large tumor size and adjacent critical structures, hypo-fractionated SRT is highly recommended.
ª 2011 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V.
Introduction
Meningioma is the most common primary brain tumors, accounting for approximately 14–20% of non-glial brain tu-mors. Although they are usually benign, they can be associated with significant morbidity when encroaching on sensitive struc-tures such as cranial nerves[1,2].
Surgery remains the mainstay of treatment with excellent lo-cal control, but may be limited by the size and site of tumor. The risk of cranial nerve palsies and other morbidities remains sig-nificant despite recent advances in microsurgical techniques[3]. * Corresponding author. Address: Children’s Cancer Hospital, Egypt.
Tel.: +20 149932166/10 25351500x1190; fax: +20 2 23619036. E-mail address:[email protected](E. Eldebawy).
1110-0362 ª 2011 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V.
Peer review under responsibility of Cairo University. doi:10.1016/j.jnci.2011.09.006
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Journal of the Egyptian National Cancer Institute
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Post operative radiotherapy (PORT) after subtotal resection has the potential to improve outcome and to increase survival rates [4,5]. In order to reduce radiation induced side effects and to increase local control, sophisticated treatment planning like stereotactic fractionated radiotherapy (SRT), stereotactic radiosurgery (SRS) and intensity modulated radiotherapy is recommended[6–8]. These techniques have enabled improved conformation of the treatment volume to the target, which is often small, of complex shape, and close to critical structures such as the brain stem, pituitary, and optic chiasma.
The aim of this work is to report our experience with stereo-tactic radiosurgery (SRS) and hypo-fractionated stereostereo-tactic radiotherapy (SRT) in the treatment of benign meningiomas with respect to local control, radiation-induced side effects, and overall survival.
Patients and methods
This is a retrospective study of 32 patients with intracranial benign meningioma who were treated with stereotactic radio-surgery (SRS) (19 patients), and hypo-fractionated stereotactic radiotherapy (SRT) (13 patients) during the period from 2003 to 2010 at the National Cancer Institute, Cairo university, Egypt. All patients were evaluated before treatment by MRI. Max-imal tumor diameter, tumor volume and distance to critical neural structures (optic pathway or brain stem) were assessed in all cases. Tumor with radiological well defined lesion, small volume (approximately less than 20 cc) and away from critical structures were candidates for stereotactic radiosurgery. Le-sions with large volume and/or involving (or adjacent to) crit-ical structures (brain stem and optic chiasma) were treated with hypo-fractionated SRT. The Karnofsky performance sta-tus (KPS) was recorded at the beginning of treatment and dur-ing follow up.
Treatment methods
Patient immobilization was achieved using Brown–Roberts– Wells (BRW) stereotactic localization frame in SRS, and Gill– Thomas–Cosmin (GTC) frame in hypo-fractionated SRT with repositioning accuracy <2 mm according to published data [9,10].
Treatment planning was performed on a three-dimensional CT data generated from continuous 2-mm CT scans. MRI scans were obtained in the treatment position. CT and MRI fusion was carried out using the three-dimensional planning system Radionics (X-Knife version 2). After stereotactic image fusion, the target volume and organs at risk, such as the eyes, optic nerves, chiasma and brain stem, were delineated on each slice of the three dimensional data. The planning target volume included the macroscopic tumor visible on MRI with a safety margin 2 mm in hypo-fractionated stereotactic radiotherapy (SRT) and no margin in stereotactic radiosurgery (SRS). Opti-mal dose distribution within the target volume and miniOpti-mal dose to normal brain and critical structures were achieved with fixed non coplanar beams using either multi leaf collimator (leaf width 2 mm at the isocenter) or cones with different sizes. Treatment was delivered with 6 MV linear accelerator. The tumor margin dose was 11-12 GY in SRS patients and 2520 cGY in 6 fractions in hypo-fractionated SRT (equivalent to 50 GY/25 F/calculated for a/b = 2). Evaluation of treat-ment planning was carried out by isodose line distribution,
dose volume histogram and target dose conformity. The pre-scription isodose volume to target volume ratio (PITV) is used by the Radiation Therapy Oncology Group (RTOG) to de-scribe the conformity of prescription isodose line to the target volume. An exemplary treatment plan with beam’s eye view is shown inFig. 1.
Follow up included radiologic (CT/MRI), clinical and neu-rologic examinations at 3 and 6 months after radiotherapy, then once a year. Radiologic tumor response was assessed after exact image fusion and measured volumetrically by use of fused thin slice MRI data sets. Tumor volume shrinkage was analyzed three dimensionally and quantitatively by use of planning system. If this procedure was not available, the tumor diameters were compared in 3 dimensions. Ophthalmologic examination and visual field perimetry in sellar and parasellar meningioma was performed after 6 months and then annually after radiotherapy. Side effects were assessed as either acute or late phenomena according to the Radiation Therapy Oncology Group (RTOG) morbidity criteria[11]. A toxic effect was con-sidered to be acute if it occurred within the first 90 days after start of treatment, and was considered late if it occurred after 90 days from the start of treatment.
Overall survival was calculated from the date of starting radiotherapy until the date of death or the date of last follow up, and progression free survival was calculated from the date of starting radiotherapy until the date of first progression or the date of last follow up.
Statistical methods
Statistical analysis was done using SPSS win statistical pack-age version 15, estimates of the survival rates (cumulative over-all survival and progression free survival) were calculated using the Kaplan–Meier product-limit method and presented as cumulative survival and standard error at the end of follow up period.
Results
They were 25 female patients and 7 males. The median age was 44 years (range 21–67 years). Fourteen patients underwent SRS or SRT as their primary treatment while 18 patients underwent post operative SRS or SRT. The histological or radiological diagnosis of benign meningioma was confirmed in all patients.Table 1shows the patients characteristics.
Median follow up period was 39 months (range 6–72 months). Symptoms of increased intracranial pressure (headache, vomiting and blurring of vision) were the most commonly encountered seen in 75% (24/32) of the patients, followed by neurological deficits (motor weakness, impaired sensation and nerve affection) detected in 63% (20/32) of the patients. Convulsion was encoun-tered in 22% (7/32 patients), while hormone deficit was seen in 6% (2/32) of the patients. All patients were (KPS) more than 70. In 31% (10/32) of the patients, preexisting neurologic symp-toms improved, 63% (20/32) remained unchanged and 6% (two patients) get worse.
Table 2shows the distribution of 32 patients according to the site of the lesions. Sellar and parasellar lesions were the most common (31%) followed by lobar lesions (28%). The total number of all treated lesions was 36 lesions.
The tumor volume ranged from 1 to 39.7 cc, with a median of 8.5 cc. Dose delivery was normalized to isodose line ranged
from 55% to 94%, the median being 85% isodose line. The volume of lesion covered with the prescribed dose ranged from 86% to 99.5%, the median being 94%. The number of nonco-planar arcs ranged from 4 to17 arcs, the median being 6 arcs. All patients were treated with PITV ratio less than 2 (Fig. 2).
Stable disease based on MRI was seen in 20/32 (63%) patients, while 10/32 (31%) patients had a reduction of tumor volume of >50% and 2/32 (6%) patient had a progression of tumor volume of >25% during follow up period.
Two patients died 6 and 7 months after end of treatment due to cardiac failure while one patient died from disease pro-gression 32 months after end of treatment. The cumulative overall survival rate for the whole group was 90 ± 5% at 5 years, (Fig. 3). Overall tumor growth control at the last follow up was observed in 30 patients. Cumulative progression free survival (PFS) at 5 years was 94 ± 4%, (Fig. 4). Two patients exhibited tumor progression; both of them had para-sellar meningioma.
Acute toxicity was mild and consisted of mild headache, transient tinnitus or general weakness in 8/32 (25%) patients. Short term course of corticosteroids therapy (<3 months) Table 1 Patient’s characteristics.
Age (year) Median 44 Range 21–67 Sex (No.%) Female 25 (78%) Males 7 (22%) Follow up (months) Median 39 Range 6–72 Tumor volume (cc) Median 9.2 Range 1.8–39.7
Treatment groups (No.% of patients)
SRS 19 (59%)
Hypo-fractionated SRT: 13 (41%)
Types of treatment (No.% of patients)
Primary 14 (44%)
PORT 18 (56%)
Figure 1 Exemplary treatment plan. (a) Observer’s view of tumor and organ at risk. (b) Transverse view. (c) Coronal view. (d) Sagittal view.
Table 2 Distribution of 32 patients according to the site of the lesions.
Site Frequency (n = 32) Percentage
Sellar & parasellar 10 31
Lobar 9 28
Cavernous sinus 5 16
was given to 3/32 (9.3%) patients. Visual field deterioration was seen in 2/32 (6.2%) patients, one of them was due to disease progression. No patient developed hypothalamic–pituitary dysfunction. No sign of increased intracranial pressure due to post radiation therapy oedema was detected in our patients. No late toxicity was detected within the follow up period.
Discussion
An increasing number of reports concerning SRS and SRT as an adjuvant treatment or as an alternative therapy to aggressive microsurgery have been published. SRT given after incomplete resection of primary or recurrent meningioma or as first line treatment has been shown to improve tumor control compared with outcomes in patients treated by surgery alone[12–17].
More recently, several studies have reported encouraging results on SRS treatment for benign meningioma. Despite the objections raised after the publications of preliminary results of this technique, long term evaluation of SRS in meningioma treatment has demonstrated an improved tumor control whether used as first line or post resection adjuvant treatment[18–20].
The 5 year PFS rate for 32 patients with benign meningi-oma treated by SRS and SRT in our department was 94%. These data are nearly comparable with other reports[21–25]: Selch et al. reported a 3-year progression free survival of 97.4% in 45 patients treated for benign meningiomas with fractionated stereotactic radiotherapy[21]. Jalali et al. with a median follow up of 21 months has reported no recurrences in 41 patients treated with SRT[22]. The largest study to date was introduced by Debus et al. A total number of 189 patients treated with fractionated stereotactic radiotherapy with a med-ian follow up of 35 months have been followed; local control was excellent, with only 3 patients recurring[23].
Single fraction stereotactic radiosurgery has also been used extensively to treat skull base meningiomas with similar high levels of local control. Lee et al. reported a series of 159 patients with cavernous sinus meningiomas treated with gam-ma knife radiosurgery showing local control of 93% with a median follow up of 35 months[24]. Shafron et al. treated 70 benign meningiomas with a mean follow up of 23 months showing a 100% control rate[25].
Our results are better than the results achieved in microsur-gical series with available follow up[26–28]. In the two princi-pal microsurgical series, the PFS rate ranged from 61.5% to 80.7% with a mean follow up inferior to 4 year[26,27].
On the basis of different definitions and preconditions, the data for radiologic tumor response is very heterogeneous. Tumor volume shrinkage was published between 13% and 61%[29–32]. If not measured volumetrically (by use of fused thin slice MRI data sets), the interpretation of these results appears to be very difficult. Most of the authors define regres-sion as 2 mm shrinkage in tumor diameter, but to have MRI images with exactly the same slice angulations available is rare, even though they are needed for exact comparison[33,34]. In our patient group, in respect to our definition of tumor volume shrinkage/enlargement, tumor shrinkage (reduction of tumor volume of >50%) was observed in 31% of patients.
In comparing our study to those of other authors, we ob-served an unchanged (63%) and improved (31%) clinical status. Only 2 of 32 patients (6%) showed worsening conditions. Higher [33,34] and lower[25,31,32]worsening rates were published. Conclusion
SRS and SRT are effective and safe treatment modality for local control of meningioma with low risk of significant acute and late toxicity. In case of large tumor size and adjacent critical structures SRT is highly recommended.
Figure 2 The distribution of brain lesions as regards the PITV ratio.
Figure 3 Cumulative overall survival of 32 patients with benign intracranial meningioma.
Figure 4 Cumulative progression free survival of 32 patients with benign intracranial meningioma.
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